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Pulmonary drug delivery

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https://www.readbyqxmd.com/read/28445938/pirfenidone-normalizes-the-tumor-microenvironment-to-improve-chemotherapy
#1
Christiana Polydorou, Fotios Mpekris, Panagiotis Papageorgis, Chrysovalantis Voutouri, Triantafyllos Stylianopoulos
Normalization of the tumor microenvironment by selectively targeting components of the tumor extracellular matrix has been recently proposed to have the potential to decompress tumor blood vessels, increase vessel perfusion and thus, improve drug delivery and the efficacy of cancer therapy. Therefore, we now need to identify safe and well tolerated pharmaceutical agents that are able to remodel the microenvironment of solid tumors and enhance chemotherapy. In this study, we repurposed Pirfenidone, a clinically approved anti-fibrotic drug for the treatment of idiopathic pulmonary fibrosis, to investigate its possible role on tumor microenvironment normalization...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28435870/nanoparticles-that-do-not-adhere-to-mucus-provide-uniform-and-long-lasting-drug-delivery-to-airways-following-inhalation
#2
Craig S Schneider, Qingguo Xu, Nicholas J Boylan, Jane Chisholm, Benjamin C Tang, Benjamin S Schuster, Andreas Henning, Laura M Ensign, Ethan Lee, Pichet Adstamongkonkul, Brian W Simons, Sho-Yu S Wang, Xiaoqun Gong, Tao Yu, Michael P Boyle, Jung Soo Suk, Justin Hanes
Mucoadhesive particles (MAP) have been widely explored for pulmonary drug delivery because of their perceived benefits in improving particle residence in the lungs. However, retention of particles adhesively trapped in airway mucus may be limited by physiologic mucus clearance mechanisms. In contrast, particles that avoid mucoadhesion and have diameters smaller than mucus mesh spacings rapidly penetrate mucus layers [mucus-penetrating particles (MPP)], which we hypothesized would provide prolonged lung retention compared to MAP...
April 2017: Science Advances
https://www.readbyqxmd.com/read/28435772/self-assembled-bifunctional-peptide-as-effective-drug-delivery-vector-with-powerful-antitumor-activity
#3
Rangrang Fan, Lan Mei, Xiang Gao, Yuelong Wang, Mingli Xiang, Yu Zheng, Aiping Tong, Xiaoning Zhang, Bo Han, Liangxue Zhou, Peng Mi, Chao You, Zhiyong Qian, Yuquan Wei, Gang Guo
E-cadherin/catenin complex is crucial for cancer cell migration and invasion. The histidine-alanine-valine (HAV) sequence has been shown to inhibit a variety of cadherin-based functions. In this study, by fusing HAV and the classical tumor-targeting Arg-Gly-Asp (RGD) motif and Asn-Gly-Arg (NGR) motif to the apoptosis-inducing peptide sequence-AVPIAQK, a bifunctional peptide has been constructed with enhanced tumor targeting and apoptosis effects. This peptide is further processed as a nanoscale vector to encapsulate the hydrophobic drug docetaxel (DOC)...
April 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28428618/pulmonary-delivery-of-triptolide-loaded-liposomes-decorated-with-anti-carbonic-anhydrase-ix-antibody-for-lung-cancer-therapy
#4
Congcong Lin, Blenda Chi Kwan Wong, Hubiao Chen, Zhaoxiang Bian, Ge Zhang, Xue Zhang, Muhammad Kashif Riaz, Deependra Tyagi, Ge Lin, Yanbo Zhang, Jinjin Wang, Aiping Lu, Zhijun Yang
Antibody-decorated liposomes can facilitate the precise delivery of chemotherapeutic drugs to the lung by targeting a recognition factor present on the surface of lung tumor cells. Carbonic anhydrase IX (CA IX) is an enzyme expressed on the surface of lung cancer cells with a restricted expression in normal lungs. Here, we explored the utility of anti-carbonic anhydrase IX (CA IX) antibody, conjugated to the surface of triptolide (TPL)-loaded liposomes (CA IX-TPL-Lips), to promote the therapeutic effects for lung cancer via pulmonary administration...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424536/rifapentine-linezolid-loaded-plga-microspheres-for-interventional-therapy-of-cavitary-pulmonary-tuberculosis-preparation-and-in-vitro-characterization
#5
Jieyun Huang, Zhi Chen, Ying Li, Li Li, Guangyu Zhang
In this study, we aimed to design controlled-release microspheres for the treatment of cavitary pulmonary tuberculosis (TB) for solving the issues of poor drug delivery and short duration maintained at effective drug concentration during bronchoscopic interventional therapy. We fabricated rifapentine-linezolid-loaded poly(lactic acid-co-glycolic acid) microspheres (RLPMs) using the oil-in-water emulsion solvent evaporation method and assessed their in vitro release as well as the bronchial mucosal retention characteristics...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28418758/inhaled-heparin-therapeutic-efficacy-and-recent-formulations
#6
Ayca Yildiz-Pekoz, Yildiz Ozsoy
Heparin is well known for its anticoagulant and anti-inflammatory properties. Inhaled heparin regimens are increasingly being used to manage lung disease. It has been used to treat cystic fibrosis, thromboembolism, and pulmonary fibrosis, as well as bronchial asthma and asthma-induced airway hypersensitivity. Several preclinical studies attained some useful effects of heparin-administered, parenterally and through inhalation, treatment of lung disease. Besides, recent clinical trials suggest that inhaled heparin for lung diseases is beneficial and safe, but such data remain to be limited...
April 18, 2017: Journal of Aerosol Medicine and Pulmonary Drug Delivery
https://www.readbyqxmd.com/read/28415888/bioengineered-gold-nanoparticles-targeted-to-mesenchymal-cells-from-patients-with-bronchiolitis-obliterans-syndrome-does-not-rise-the-inflammatory-response-and-can-be-safely-inhaled-by-rodents
#7
Emanuela Cova, Simona Inghilleri, Laura Pandolfi, Monica Morosini, Sara Magni, Miriam Colombo, Davide Piloni, Chiara Finetti, Gabriele Ceccarelli, Laura Benedetti, Maria Gabriella Cusella, Manuela Agozzino, Fabio Corsi, Raffaele Allevi, Simona Mrakic-Sposta, Sarah Moretti, Simona De Gregori, Davide Prosperi, Federica Meloni
The use of gold nanoparticles as drug delivery system represents a promising issue for diseases without effective pharmacological treatment due to insufficient local drug accumulation and excessive systemic toxicity. Bronchiolitis obliterans syndrome (BOS) represents about 70% of cases of chronic lung allograft dysfunction, the main challenge to long term lung transplantation. It is believed that due to repeated insults to epithelial bronchiolar cells local inflammatory response creates a milieu that favours epithelial mesenchymal transition and activation of local mesenchymal cells leading to airway fibro-obliteration...
April 18, 2017: Nanotoxicology
https://www.readbyqxmd.com/read/28415455/heparin-modified-graphene-oxide-for-ph-sensitive-sustained-release-of-doxorubicin-hydrochloride
#8
Baomei Zhang, Xiaoye Yang, Yang Wang, Guangxi Zhai
A novel nanocarrier of heparin (Hep) modified graphene oxide (GO) was fabricated via a linker (adipic dihydrazide) and used as a pH-sensitive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for anti-tumor therapy. The finally obtained nanocarrier was GO-ADH-Hep with better stability, blood compatibility and biocompatibility confirmed by the hemolytic test and in vitro cytotoxicity study. Its safety issue was greatly improved via Hep modification. The amount of DOX loaded onto GO-ADH-Hep was significantly high and dependent on pH value...
June 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28410199/chronic-intratracheal-application-of-the-soluble-guanylyl-cyclase-stimulator-bay-41-8543-ameliorates-experimental-pulmonary-hypertension
#9
Matthieu Amirjanians, Bakytbek Egemnazarov, Akylbek Sydykov, Baktybek Kojonazarov, Ralf Brandes, Himal Luitel, Kabita Pradhan, Johannes-Peter Stasch, Gorden Redlich, Norbert Weissmann, Friedrich Grimminger, Werner Seeger, Hossein Ghofrani, Ralph Schermuly
Dysfunction of the NO/sGC/cGMP signaling pathway has been implicated in the pathogenesis of pulmonary hypertension (PH). Therefore, agents stimulating cGMP synthesis via sGC are important therapeutic options for treatment of PH patients. An unwanted effect of this novel class of drugs is their systemic hypotensive effect. We tested the hypothesis that aerosolized intra-tracheal delivery of the sGC stimulator BAY41-8543 could diminish its systemic vasodilating effect.Pharmacodynamics and -kinetics of BAY41-8543 after single intra-tracheal delivery was tested in healthy rats...
March 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28394614/a-synthetic-macromolecular-antibiotic-platform-for-inhalable-therapy-against-aerosolized-intracellular-alveolar-infections
#10
Debobrato Das, Jasmin Chen, Selvi Srinivasan, Abby Michelle Kelly, Brian Lee, Hye-Nam Son, Frank Radella, Timothy E West, Daniel M Ratner, Anthony J Convertine, Shawn J Skerrett, Patrick S Stayton
Lung-based intracellular bacterial infections remain one of the most challenging infectious disease settings. For example, the current standard for treating Franciscella tularensis pneumonia (tularemia) relies on prolonged administration of oral and intravenous antibiotics that poorly achieve and sustain pulmonary drug bioavailability. Inhalable antibiotic formulations are approved and in clinical development for upper respiratory infections, but sustained drug dosing from inhaled antibiotics against alveolar intracellular infections remains a current unmet need...
April 10, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28377314/clarithromycin-and-n-acetylcysteine-co-spray-dried-powders-for-pulmonary-drug-delivery-a-focus-on-drug-solubility
#11
Michele Dario Manniello, Pasquale Del Gaudio, Rita P Aquino, Paola Russo
Cystic fibrosis (CF) lungs are usually susceptible to Pseudomonas aeruginosa colonization and this bacterium is resistant to immune system clearance and drug control. Particularly, the biofilm mode of growth protects several microorganisms from host defenses and antibacterial drugs, mainly due to a delayed penetration of the drug through the biofilm matrix. Biofilm, together with lung mucus viscosity and tenacity, reduces, therefore, the effectiveness of conventional antibiotic therapy in CF. The aim of this research was to design and develop a stable, portable, easy to use dry powder inhaler (DPI) for CF patients, able to release directly to the lung an association of macrolide antibiotics (clarithromycin) and a mucolytic agent (N-Acetyl-Cysteine)...
April 1, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28373109/modelling-the-bronchial-barrier-in-pulmonary-drug-delivery-a-human-bronchial-epithelial-cell-line-supplemented-with-human-tracheal-mucus
#12
Xabi Murgia, Hanzey Yasar, Cristiane Carvalho-Wodarz, Brigitta Loretz, Sarah Gordon, Konrad Schwarzkopf, Ulrich Schaefer, Claus-Michael Lehr
The airway epithelium together with the mucus layer coating it forms a protective system that efficiently filters and removes potentially harmful particles contained in inhaled air. The same mechanism, however, serves to entrap particulate drug carriers, precluding their interaction with their target. The mucus barrier is often neglected in in vitro testing setups employed for the assessment of pulmonary drug delivery strategies. Therefore, our aim was to more accurately model the bronchial barrier, by developing an in vitro system comprising a tight epithelial cell layer which may be optionally supplemented with a layer of human tracheal mucus...
April 1, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28367654/a-review-of-co-milling-techniques-for-the-production-of-high-dose-dry-powder-inhaler-formulation
#13
Michael Lau, Paul M Young, Daniela Traini
Drug delivery by inhalation offers several advantages compared to other dosage forms, including rapid clinical onset, high bioavailability, and minimal systemic side effects. Drug delivery to the lung can be achieved as liquid suspensions or solutions in nebulizers and pressurized metered-dose inhalers (pMDI), or as dry powders in dry powder inhalers (DPIs). Compared to other delivery systems, DPIs are, in many cases, considered the most convenient as they are breath actuated and do not require the use of propellants...
April 19, 2017: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/28363142/local-co-administration-of-gene-silencing-rna-and-drugs-in-cancer-therapy-state-of-the-art-and-therapeutic-potential
#14
REVIEW
Mikael Larsson, Wei-Ting Huang, Dean-Mo Liu, Dusan Losic
Gene-silencing miRNA and siRNA are emerging as attractive therapeutics with potential to suppress any genes, which could be especially useful in combination cancer therapy to overcome multidrug resistant (MDR) cancer. Nanomedicine aims to advance cancer treatment through functional nanocarriers that delivers one or more therapeutics to cancer tissue and cells with minimal off-target effects and suitable release kinetics and dosages. Although much effort has gone into developing circulating nanocarriers with targeting functionality for systemic administration, another alternative and straightforward approach is to utilize formulations to be administered directly to the site of action, such as pulmonary and intratumoral delivery...
March 16, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28347847/dry-powder-inhaler-performance-of-spray-dried-mannitol-with-tailored-surface-morphologies-as-carrier-and-salbutamol-sulphate
#15
M Mönckedieck, J Kamplade, P Fakner, N A Urbanetz, P Walzel, H Steckel, R Scherließ
Nowadays, dry powder inhalation as applied in the therapy of pulmonary diseases is known as a very effective route of drug delivery to the lungs. Here, the system of coarse carrier and fine drug particles attached to the carrier surface has successfully been applied to overcome the cohesiveness of small drug particles. Particle properties of both carrier and drug are known to affect drug dispersion as has widely been discussed for lactose monohydrate and various drugs. This study utilises particle-engineered mannitol as an alternative carrier to discover the effect of mannitol carrier particle properties like particle shape, surface roughness, flowability or particle size on aerodynamic performance during inhalation...
March 24, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28336457/synergistic-inhibition-of-migration-and-invasion-of-breast-cancer-cells-by-dual-docetaxel-quercetin-loaded-nanoparticles-via-akt-mmp-9-pathway
#16
Jing Li, Jun Zhang, Yiyue Wang, Xiao Liang, Zaitongguli Wusiman, Yunzhi Yin, Qi Shen
Metastasis impedes the successful chemotherapy for breast cancer. In this study, an Akt inhibitor (quercetin, Qu) was co-delivered with a chemotherapeutic agent (docetaxel, DTX) by using hyaluronic acid (HA)-modified nanoparticles (NPs) as vectors to block metastasis. Dual DTX/Qu-loaded HA/polylactic-co-glycolic acid-polyethyleneimine NPs (PP-HA/NPs) were prepared through a modified emulsion solvent evaporation technique. The particle size of PP-HA/NPs with narrow polydispersity was 209.8±10.8nm. Wound healing assay revealed that Qu co-delivery and HA modification elicited synergistic inhibitory effects on cell motility...
March 21, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28322939/do-we-need-to-study-metabolism-and-distribution-in-the-eye-why-when-and-are-we-there-yet
#17
Upendra A Argikar, Jennifer L Dumouchel, Valerie M Kramlinger, Amanda L Cirello, Mithat Gunduz, Christine E Dunne, Bindi Sohal
Liver is known to be the principal site of drug metabolism. Depending on the route of administration, especially in cases of topical/local delivery, evaluation of local drug metabolism in extrahepatic tissues is vital to assess fraction metabolized. This parameter becomes important from the point of view of drug availability or the contribution to overall clearance. Examples include fraction metabolized in the gut for oral drugs and contribution of pulmonary or renal clearance to total clearance of a drug. Diseases of the eye represent a rising unmet medical need, and a number of therapeutics are currently being developed in the form of small molecules and biologics...
March 17, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28304180/nanomedicine-for-the-treatment-of-acute-respiratory-distress-syndrome-the-2016-ats-bear-cage-award-winning-proposal
#18
Jacob S Brenner
After dozens of clinical trials, there are still no Food and Drug Administration-approved drugs that improve mortality in acute respiratory distress syndrome (ARDS). These poor results may be caused in part by three unique pharmacological challenges presented by ARDS: (1) Patients with ARDS are fragile because of concomitant multiple organ dysfunction, so they do not tolerate off-target side effects of drugs; (2) inhaled drug delivery is impeded by the column of proteinaceous fluid covering the injured alveoli; and (3) ARDS is heterogeneous in its underlying pathophysiology, so targeting one pathway is unlikely to improve most patients...
April 2017: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/28303966/targeted-delivery-of-doxorubicin-by-nano-loaded-mesenchymal-stem-cells-for-lung-melanoma-metastases-therapy
#19
Yuekui Zhao, Shanshan Tang, Jiamin Guo, Murad Alahdal, Shunxiu Cao, Zhaocong Yang, Fangfang Zhang, Yumeng Shen, Minjie Sun, Ran Mo, Li Zong, Liang Jin
Poor antigenic presentation of tumor tissues and a lack of specific targets currently limit the success of nanoparticle delivery system. Cellular carrier technique has been recently explored extensively as a substitutive or supplement for traditional targeting delivery system. Here, we demonstrate the usage of mesenchymal stem cells (MSCs) loaded with doxorubicin containing polymer nanoparticles in pulmonary melanoma metastases therapy, as a modified technique of targeted delivery system. The characterizations of prepared nanoparticles and MSCs sensitivity to DOX and PLGA-DOX were measured...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28284323/optimizing-drug-delivery-in-copd-the-role-of-inhaler-devices
#20
REVIEW
Paola Rogliani, Luigino Calzetta, Angelo Coppola, Francesco Cavalli, Josuel Ora, Ermanno Puxeddu, Maria Gabriella Matera, Mario Cazzola
Inhaled medication is the cornerstone of the pharmacological treatment for patients with asthma and chronic obstructive pulmonary disease (COPD). Several inhaler devices exist, and each device has specific characteristics to achieve the optimal inhalation of drugs. The correct use of inhaler devices is not granted and patients may incur in mistakes when using pressurized metered-dose inhalers (pMDIs) or dry-powder inhaler (DPIs). The incorrect use of inhaler devices can lead to a poorly controlled disease status...
March 2017: Respiratory Medicine
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